Real-life ankle submovements and computer mouse use reflect patient-reported function in adult ataxias

Abstract Novel disease-modifying therapies are being evaluated in spinocerebellar ataxias and multiple system atrophy. Clinician-performed disease rating scales are relatively insensitive for measuring disease change over time, resulting in large and long clinical trials. We tested the hypothesis that sensors worn continuously at home during natural behaviour and a web-based computer mouse task performed at home could produce interpretable, meaningful and reliable motor measures for potential use in clinical trials. Thirty-four individuals with degenerative ataxias (spinocerebellar ataxia types 1, 2, 3 and 6 and multiple system atrophy of the cerebellar type) and eight age-matched controls completed the cross-sectional study. Participants wore an ankle and wrist sensor continuously at home for 1 week and completed the Hevelius computer mouse task eight times over 4 weeks. We examined properties of motor primitives called ‘submovements’ derived from the continuous wearable sensors and properties of computer mouse clicks and trajectories in relationship to patient-reported measures of function (Patient-Reported Outcome Measure of Ataxia) and ataxia rating scales (Scale for the Assessment and Rating of Ataxia and the Brief Ataxia Rating Scale). The test–retest reliability of digital measures and differences between ataxia and control participants were evaluated. Individuals with ataxia had smaller, slower and less powerful ankle submovements during natural behaviour at home. A composite measure based on ankle submovements strongly correlated with ataxia rating scale scores (Pearson’s r = 0.82–0.88), strongly correlated with self-reported function (r = 0.81), had high test–retest reliability (intraclass correlation coefficient = 0.95) and distinguished ataxia and control participants, including preataxic individuals (n = 4) from controls. A composite measure based on computer mouse movements and clicks strongly correlated with ataxia rating scale total (r = 0.86–0.88) and arm scores (r = 0.65–0.75), correlated well with self-reported function (r = 0.72–0.73) and had high test–retest reliability (intraclass correlation coefficient = 0.99). These data indicate that interpretable, meaningful and highly reliable motor measures can be obtained from continuous measurement of natural movement, particularly at the ankle location, and from computer mouse movements during a simple point-and-click task performed at home. This study supports the use of these two inexpensive and easy-to-use technologies in longitudinal natural history studies in spinocerebellar ataxias and multiple system atrophy of the cerebellar type and shows promise as potential motor outcome measures in interventional trials.

MEMS sensor (range: +/-8g; res: 12bit). The study supplies were mailed to the participant's home address. Participants began the wear-period after being guided by a study coordinator on how to properly wear and activate the devices during the initial Zoom video conference call. The devices were set up so that once they were activated, they were unable to be turned off. Participants were asked to wear these devices continuously for one week and were reminded that they were waterproof and should be worn while sleeping. The small and lightweight device could be worn continuously for the week without the need to recharge or download data from the device. The wrist device, worn like a watch with a waterproof rubber band, included an adjustable strap to ensure the device was securely fastened on the wrist. Originally, the cloth ankle band that was worn was fastened with velcro and would occasionally cause skin irritation. Four participants reported discomfort with the original band, so this was replaced with a more comfortable band that was used by participants 14-42. Zero of the last 29 participants experienced discomfort with the new ankle band. The ankle device was placed inside of a fabric band with secure snap buttons so it could be worn comfortably around the ankle. Of note, the algorithms used in data analysis do not require the sensor to be oriented a specific way, thus the motor measures were tolerant to errors in placement. Although the GENEactiv device was chosen for use in this study, since only triaxial accelerometer data were used, there is potential for the same motor measures to be obtained from other similar devices.

Questionnaires
Study questionnaires listed below were collected and managed using REDCap 1 electronic data capture tools hosted at MGH.

Rand 36 Item Short Form Health Survey:
The Rand Short Form 36 2 is a 36-item patient-reported health survey that covers health realms domains of physical functioning, emotional well-being, energy/fatigue, social functioning, pain, and general health.
The EQ-VAS (Visual Analog Scale) is a patient-reported visual scale that assesses a patient's current health on a scale from 0 (worst imaginable health) to 100 (best imaginable health).

Neuro-QOL Fatigue scale:
The Neuro-QOL Fatigue subscale 5 is a brief, 8-item scale used to assess participants' feelings of fatigue over the period of the past 7 days.

Study Feedback Survey:
This survey was administered to all participants in the study, regardless of completion status. The survey asked the participants their opinions on each of the study task's difficulty level, time commitment, and instruction clarity, the setting and device(s) used to complete each study task, and whether they experienced any problems while completing each task.
At the end of the survey, participants selected symptoms that they typically experience (from a list of common symptoms of SCA and MSA), and were asked to rate if the study tasks were able to capture each symptom (on a scale including 2, Yes/mostly; 1, possibly/unsure; or 0, No/not really).
They then had the opportunity to provide comments for the study team. Supplementary Table 1. PROM-Ataxia subscores. Motor, symptoms, emotion, and cognition subscores were taken directly from Schmahmann et al., 6 whereas arm and gait/balance subscores were generated based on the PROM-Ataxia questions listed.

Motor
Labeled as "Physical" in Section 2 of PROM-Ataxia

Symptoms
Labeled as "Physical" in Section 1 of PROM-Ataxia

Emotion
Labeled as "Mental" in Section 1 of PROM-Ataxia

Cognition
Labeled as "Mental" in Section 2 of PROM-Ataxia Arm score (constructed)